RESUMO
Leukotriene B4 (LTB4) is one of the most potent chemotactic compounds produced in macrophages and neutrophils. LTB4 is a product of arachidonic acid oxygenation by 5-lipoxygenase pathway. We present here the data on regulation of LT synthesis in human polymorphonuclear leukocytes by cholesterol, cholesterol sulfate and cholesterol phosphate. The addition of Pseudomonas aeruginosa lipopolysaccharides (LPS) with lipid vesicles containing phosphatidylcholine or phosphatidylcholine/cholesterol (70:30) showed that omitting cholesterol abolished the effect of LPS on LT synthesis. We show here the capacity of cholesterol sulfate, the most abundant sulfated sterol in human blood, to suppress LT production in human neutrophils and to neutralize the effect of P. aeruginosa LPS on LT synthesis. We suggest that sulfated lipids serve as specific endogenous regulators of LT synthesis in neutrophils, and anti-inflammatory therapy may be based on modification of cholesterol level and its conversion to anionic derivatives.
Assuntos
Colesterol/fisiologia , Leucotrieno B4/biossíntese , Lipídeos/fisiologia , Neutrófilos/metabolismo , Araquidonato 5-Lipoxigenase/metabolismo , Humanos , Leucotrieno B4/metabolismo , Leucotrienos/biossíntese , Metabolismo dos Lipídeos/fisiologia , Lipopolissacarídeos/metabolismo , Fosfolipídeos/fisiologiaRESUMO
The effect of 10(-14)-10(-4)M ibuprofen and aspirin both on arachidonic acid metabolism in peritoneal murine macrophages and on the concanavalin A-induced proliferation of murine splenocytes were investigated. It was shown that 10(-7)-10(-4)M ibuprofen inhibits the arachidonic acid metabolism. On the other hand, 10(-12)-10(-11)M ibuprofen causes pronounced activation of arachidonic acid metabolism. The low concentration (10(-14)-10(-10)M) effects also take place when non-steroidal anti-inflammatory drugs influence other functions of the immune system: that is, they activate the splenocyte mitogen-induced proliferative response. These results are in accord with our suggestion that the low concentration effects of these drugs do not depend upon cell types and may have an important physiological significance.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Ácido Araquidônico/metabolismo , Ativação Linfocitária/efeitos dos fármacos , Macrófagos Peritoneais/efeitos dos fármacos , Animais , Aspirina/farmacologia , Relação Dose-Resposta a Droga , Ibuprofeno/farmacologia , Macrófagos Peritoneais/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos CBARESUMO
The influence of morphine on proliferation of human tumor K562 and lymphoid cells was studied and compared with that on the mitogen-induced proliferation of human peripheral blood mononuclear cells (PBMC). Morphine was shown to act as a suppressor of both cellular DNA synthesis (50% and more as compared to control) and the cellular population growth of mitogen-induced PBMC, B-lymphoma Namalva cells and EBV-transformed lymphocytes. Morphine activated proliferation of myeloid K562 and T-lymphoma Yurkat cells 1.5-fold. It is supposed that the opposite effects of morphine on proliferation of cell lines of immune origin reveal the difference in modulation of diverse immune cell types by morphine.
